The broad objective of the present studies is to clarify the role played by catecholamines in the regulation of metabolism, with particular emphasis on the way in which the sympathetic nervous system and the adrenal medulla work together in defense of the internal environment. Studies from our laboratory have demonstrated an important effect of dietary intake on sympathetic activity; fasting suppresses and overfeeding sucrose stimulates the sympathetic nervous system in laboratory rodents and in man. Studies are planned to elucidate the signal(s) involved in coupling changes in dietary intake with changes in sympathetic activity. In experimental animals the activity of the sympathetic nervous system is assessed by measuring the turnover rate of norepinephrine in sympathetically innervated tissues, in conjunction with measurement of catecholamine excretion and catecholamine levels in various tissues including the adrenal medulla. In human subjects sympathoadrenal activity is assessed by measurement of plasma catecholamines and the urinary excretion of catecholamines. In addition, the impact of diet on the sympathoadrenal response to a variety of physiologic and pathophysiologic states that affect metabolism will be studied. Thus cold exposure, experimental uremia, hypoxia, potassium adaptation, diabetes, and hypoglycemia along with trauma, hyper and hypothyroidism will be studied and the impact of changes in diet on sympathoadrenal activity in these situations investigated. The long term goal of this project is improved therapeutics based on a better understanding of the role of catecholamines in the regulation of metabolism in a variety of physiologic and pathophysiologic states relevant to disease in man.